title: Cosegregation of focal segmental glomerulosclerosis in a family with familial partial lipodystrophy due to a mutation in LMNA.
abstract: OBJECTIVE
  Focal segmental glomerulosclerosis (FSGS) is a common cause of idiopathic nephrotic syndrome in adults (35%). A number of genetic and familial forms of FSGS have been recognized. Here, we report a large pedigree with a pathogenic mutation in LMNA (R349W) in which four members were found to have biopsy-proven FSGS. The LMNA gene codes for lamins A and C, major components of the nuclear lamina which function in nuclear architecture, integrity and the regulation of gene expression.
  
  
  METHODS
  Pedigree screening and mutation analysis of LMNA gene in all family members. Renal biopsies were performed in proteinuric patients. A molecular 3D model of the familial LMNA mutation was constructed.
  
  
  RESULTS
  There were a total of 16 affected members from four generations, 12 of whom were found to carry the germline LMNA mutation. All affected adults had clinical features of familial partial lipodystrophy (FPLD) of the non-Dunnigan variety. Four patients within the same generation presented with a variable degree of renal impairment and proteinuria. Renal biopsies from all four revealed FSGS. The familial mutation is a missense change (R349W) in exon 6 of LMNA (c.1045C>T).
  
  
  CONCLUSIONS
  We report a genetic link between LMNA and biopsy-proven FSGS in a large pedigree with FPLD. This unexpected association extends the disease spectrum of LMNA to the kidney and suggests that the physiological role of LMNA could be relevant to the maintenance of glomerular structure and function.
authors.affiliation: Kidney Genetics Group, Academic Nephrology Unit, University of Sheffield Medical School, Sheffield, UK.
authors.forename: Kah Mean
authors.initials: KM
authors.lastname: Thong
authors.forename: Yaoxian
authors.initials: Y
authors.lastname: Xu
authors.forename: Jackie
authors.initials: J
authors.lastname: Cook
authors.forename: Anna
authors.initials: A
authors.lastname: Takou
authors.forename: Bart
authors.initials: B
authors.lastname: Wagner
authors.forename: Bisher
authors.initials: B
authors.lastname: Kawar
authors.forename: Albert C M
authors.initials: AC
authors.lastname: Ong
mesh_terms: D000328:Adult; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D052496:Lipodystrophy, Familial Partial / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A